Determination of nornicotine in smokers' urine by gas chromatography following reductive alkylation to N'-propylnornicotine

A sensitive gas chromatographic assay has been developed to measure concentrations of nornicotine in human urine. A structural analogue, 5-methylnornicotine, is used as an internal standard. Both nornicotine and the internal standard were converted to the corresponding N′-propyl derivatives using a novel reductive alkylation procedure. The N′-propyl derivatives have good chromatographic properties, which allows quantitative measurement in the low nanograms per milliliter range. Concentrations of nornicotine in smokers' urine were quantitated and compared with the concentrations of nicotine and its metabolites, cotinine, nicotine-N-oxide and cotinine-N-oxide.